Purpose :
Mutations in RPGRORF15 cause 70 to 90% of X-linked retinitis pigmentosa (XLRP), making this gene a high-yield target for therapeutic intervention. By analyzing pre-treatment characteristics in a cohort of 50 XLRP-RPGR patients, this study aims to assist future interventional trials by analyzing symmetry of disease, rate of progression and suitability of outcome measures.

Results :
Of the observed phenotypes, 96% followed rod-cone and 4% a cone-rod phenotype. 73% of exonic mutations occurred in ORF15. 80% of missense mutations clustered in exons 1-14, whereas 85% of nonsense mutations were present in ORF15. No clear genotype-phenotype relationship could be established between mutations located in exons 1-14 or ORF15. Patients with ORF15 mutations did not have a significantly different visual acuity (p = 0.9) or visual field (III4e; p = 0.6) than those with mutations in exons 1-14. Comparison of both eyes revealed a strong symmetry of degeneration in all outcome measures, with visual fields (I4e R2 = 0.99; III4e R2 = 0.9) and ERG (30 Hz flicker R2 = 0.9) exhibiting the highest symmetry. Disease progression eluded description by a simple function. Kaplan-Meier curve (KMC) estimates predicted a loss of 6/6 vision at a mean of 34 years (± 2.9; Confidence Interval), with a loss of reading ability occurring at 39 years (± 2.6) and a complete loss of vision at 48 (± 1.6) years.

Conclusions :
High symmetry in all outcome measures confirms that the contralateral eye can be used as an internal control in an RPGR-XLRP gene therapy trial. The variability between patients makes an intra-individual control preferable to an inter-individual control. According to these findings, the most sensitive parameter to measure disease progression and treatment success in an interventional RPGR-XLRP trial seems to be kinetic visual field using the III4e target. KMC analysis predicts the most severe decline in vision between the third and fourth decade of life.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.